{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:41:30Z","timestamp":1791214890450,"version":"4.1.0"},"reference-count":14,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,4,21]],"date-time":"2015-04-21T00:00:00Z","timestamp":1429574400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:sec><jats:label\/><jats:p>Isolated mitochondrial respiratory chain complex III deficiency has been described in a heterogeneous group of clinical presentations in children and adults. It has been associated with mutations in <jats:italic>MT\u2010CYB<\/jats:italic>, the only mitochondrial DNA encoded subunit, as well as in nine nuclear genes described thus far: <jats:italic>BCS1L, TTC19, UQCRB, UQCRQ, UQCRC2, CYC1, UQCC2, LYRM7<\/jats:italic>, and <jats:italic>UQCC3. BCS1L, TTC19<\/jats:italic>, <jats:italic>UQCC2, LYRM7<\/jats:italic>, and <jats:italic>UQCC3<\/jats:italic> are complex III assembly factors. We report on an 8\u2010year\u2010old girl born to consanguineous Iraqi parents presenting with slowly progressive encephalomyopathy, severe failure to thrive, significant delays in verbal and communicative skills and bilateral retinal cherry red spots on fundoscopy. SNP array identified multiple regions of homozygosity involving 7.5% of the genome. Mutations in the <jats:italic>TTC19<\/jats:italic> gene are known to cause complex III deficiency and <jats:italic>TTC19<\/jats:italic> was located within the regions of homozygosity. Sequencing of <jats:italic>TTC19<\/jats:italic> revealed a homozygous nonsense mutation at exon 6 (c.937C\u2009&gt;\u2009T; p.Q313X). We reviewed the phenotypes and genotypes of all 11 patients with <jats:italic>TTC19<\/jats:italic> mutations leading to complex III deficiency (including our case). The consistent features noted are progressive neurodegeneration with Leigh\u2010like brain MRI abnormalities. Significant variability was observed however with the age of symptom onset and rate of disease progression. The bilateral retinal cherry red spots and failure to thrive observed in our patient are unique features, which have not been described, in previously reported patients with <jats:italic>TTC19<\/jats:italic> mutations. Interestingly, all reported <jats:italic>TTC19<\/jats:italic> mutations are nonsense mutations. The severity of clinical manifestations however does not specifically correlate with the residual complex III enzyme activities. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36968","type":"journal-article","created":{"date-parts":[[2015,4,22]],"date-time":"2015-04-22T03:57:08Z","timestamp":1429675028000},"page":"1330-1336","source":"Crossref","is-referenced-by-count":37,"title":["Phenotypic variation of <i>TTC19<\/i>\u2010deficient mitochondrial complex III deficiency: A case report and literature review"],"prefix":"10.1002","volume":"167","author":[{"given":"Dylan A.","family":"Mordaunt","sequence":"first","affiliation":[{"name":"SA Pathology Women's and Children's Hospital North Adelaide Australia"},{"name":"Department of Paediatrics University of Adelaide North Adelaide Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Jolley","sequence":"additional","affiliation":[{"name":"SA Pathology Women's and Children's Hospital North Adelaide Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanti","family":"Balasubramaniam","sequence":"additional","affiliation":[{"name":"SA Pathology Women's and Children's Hospital North Adelaide Australia"},{"name":"Metabolic Unit Princess Margaret Hospital for Children Subiaco Australia"},{"name":"School of Paediatrics and Child Health The University of Western Australia Perth Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Thorburn","sequence":"additional","affiliation":[{"name":"Murdoch Childrens Research Institute and Victorian Clinical Genetics Service The Royal Children's Hospital Parkville Australia"},{"name":"Department of Paediatrics University of Melbourne Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley S.","family":"Mountford","sequence":"additional","affiliation":[{"name":"Murdoch Childrens Research Institute and Victorian Clinical Genetics Service The Royal Children's Hospital Parkville Australia"},{"name":"Department of Paediatrics University of Melbourne Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison G.","family":"Compton","sequence":"additional","affiliation":[{"name":"Murdoch Childrens Research Institute and Victorian Clinical Genetics Service The Royal Children's Hospital Parkville Australia"},{"name":"Department of Paediatrics University of Melbourne Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian","family":"Nicholl","sequence":"additional","affiliation":[{"name":"SA Pathology Women's and Children's Hospital North Adelaide Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Manton","sequence":"additional","affiliation":[{"name":"SA Pathology Women's and Children's Hospital North Adelaide Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Neurology Women's and Children's Hospital North Adelaide Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drago","family":"Bratkovic","sequence":"additional","affiliation":[{"name":"SA Pathology Women's and Children's Hospital North Adelaide Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Friend","sequence":"additional","affiliation":[{"name":"SA Pathology Women's and Children's Hospital North Adelaide Australia"},{"name":"Department of Paediatrics University of Adelaide North Adelaide Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sui","family":"Yu","sequence":"additional","affiliation":[{"name":"SA Pathology Women's and Children's Hospital North Adelaide Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,4,21]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-012-9536-4"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.32086"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2013_282"},{"key":"e_1_2_6_5_1","first-page":"583","article-title":"21. 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